Lrig1-expression confers suppressive function to CD4+ cells and is essential for averting autoimmunity via the Smad2/3/Foxp3 axis

Jae Seung Moon, Chun Chang Ho, Jong Hyun Park, Kyungsoo Park, Bo Young Shin, Su Hyeon Lee, Ines Sequeira, Chin Hee Mun, Jin Su Shin, Jung Ho Kim, Beom Seok Kim, Jin Wook Noh, Eui Seon Lee, Ji Young Son, Yuna Kim, Yeji lee, Hee Cho, Sun Hyeon So, Jiyoon Park, Eunsu ChoiJong Won Oh, Sang Won Lee, Tomohiro Morio, Fiona M. Watt, Rho Hyun Seong, Sang Kyou Lee

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Regulatory T cells (Treg) are CD4+ T cells with immune-suppressive function, which is defined by Foxp3 expression. However, the molecular determinants defining the suppressive population of T cells have yet to be discovered. Here we report that the cell surface protein Lrig1 is enriched in suppressive T cells and controls their suppressive behaviors. Within CD4+ T cells, Treg cells express the highest levels of Lrig1, and the expression level is further increasing with activation. The Lrig1+ subpopulation from T helper (Th) 17 cells showed higher suppressive activity than the Lrig1- subpopulation. Lrig1-deficiency impairs the suppressive function of Treg cells, while Lrig1-deficient naïve T cells normally differentiate into other T cell subsets. Adoptive transfer of CD4+Lrig1+ T cells alleviates autoimmune symptoms in colitis and lupus nephritis mouse models. A monoclonal anti-Lrig1 antibody significantly improves the symptoms of experimental autoimmune encephalomyelitis. In conclusion, Lrig1 is an important regulator of suppressive T cell function and an exploitable target for treating autoimmune conditions.

Original languageEnglish
Article number5382
JournalNature communications
Volume14
Issue number1
DOIs
Publication statusPublished - 2023 Dec

Bibliographical note

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© 2023, Springer Nature Limited.

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy

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